tbuckley/cabot-search huggingface dataset:
Injectable Dual‐Dynamic‐Bond Cross‐Linked Hydrogel for Highly Efficient Infected Diabetic Wound Healing
Authors: Shasha Yao, Yueqi Zhao, Yifei Xu, Biao Jin, Monian Wang, Congcong Yu, Zhengxi Guo, Shengnan Jiang, Ruikang Tang, Xiangqian Fang, Shunwu Fan
Journal: Advanced Healthcare Materials (2022)

Abstract Diabetic wound is a significant challenge for clinical treatment with high morbidity and mortality. Plenty of hydrogels with good biocompatibility have been widely used in diabetic wound healing. However, most of them cannot be directly absorbed and utilized by the wounds, which prolongs the regeneration time. Here a new type of healing hydrogel is developed that is based on histidine, a natural dietary essential amino acid that is significant for tissue formation. The amino acid is cross‐linked with zinc ions (Zn 2+ ) and sodium alginate (SA) via dynamic coordinate and hydrogen bonds, respectively, forming a histidine‐SA‐Zn 2+ (HSZH) hydrogel with good injectable, adhesive, biocompatible, and antibacterial properties. Application of this dual‐dynamic‐bond cross‐linked HSZH hydrogel accelerates the migration and angiogenesis of skin‐related cells in vitro. Furthermore, it significantly promotes the healing of infected diabetic wounds in vivo and uniquely allows a full repair of wounds within ≈13 days, while ≈27 days are required for the healing process of the control group. This work provides a new strategy for designing wound dressing materials, that weakly cross‐linked material based on tissue‐friendly micromolecules can heal the wounds more efficiently than highly cross‐linked materials based on long‐chain polymers.
A high-risk gut microbiota configuration associates with fatal hyperinflammatory immune and metabolic responses to SARS-CoV-2
Authors: Werner C. Albrich, Tarini Shankar Ghosh, Sinead Ahearn-Ford, Flora Mikaeloff, Nonhlanhla Lunjani, Brian Forde, Noémie Suh, Gian-Reto Kleger, Urs Pietsch, Manuel Frischknecht, Christian Garzoni, Rossella Forlenza, Mary Horgan, Corinna Sadlier, Tommaso Rochat Negro, Jérôme Pugin, Hannah Wozniak, Andreas Cerny, Ujjwal Neogi, Paul W. O’Toole, Liam O’Mahony
Journal: Gut Microbes (2022)

Protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and associated clinical sequelae requires well-coordinated metabolic and immune responses that limit viral spread and promote recovery of damaged systems. However, the role of the gut microbiota in regulating these responses has not been thoroughly investigated. In order to identify mechanisms underpinning microbiota interactions with host immune and metabolic systems that influence coronavirus disease 2019 (COVID-19) outcomes, we performed a multi-omics analysis on hospitalized COVID-19 patients and compared those with the most severe outcome (i.e. death, n = 41) to those with severe non-fatal disease (n = 89), or mild/moderate disease (n = 42), that recovered. A distinct subset of 8 cytokines (e.g. TSLP) and 140 metabolites (e.g. quinolinate) in sera identified those with a fatal outcome to infection. In addition, elevated levels of multiple pathobionts and lower levels of protective or anti-inflammatory microbes were observed in the fecal microbiome of those with the poorest clinical outcomes. Weighted gene correlation network analysis (WGCNA) identified modules that associated severity-associated cytokines with tryptophan metabolism, coagulation-linked fibrinopeptides, and bile acids with multiple pathobionts, such as Enterococcus. In contrast, less severe clinical outcomes are associated with clusters of anti-inflammatory microbes such as Bifidobacterium or Ruminococcus, short chain fatty acids (SCFAs) and IL-17A. Our study uncovered distinct mechanistic modules that link host and microbiome processes with fatal outcomes to SARS-CoV-2 infection. These features may be useful to identify at risk individuals, but also highlight a role for the microbiome in modifying hyperinflammatory responses to SARS-CoV-2 and other infectious agents.
NCCN Guidelines® Insights: Hematopoietic Growth Factors, Version 1.2022
Authors: Elizabeth A. Griffiths, Vivek Roy, Laura Alwan, Kimo Bachiashvili, John Baird, Rita Cool, Shira Dinner, Mark Geyer, John Glaspy, Ivana Gojo, Ashley Hicks, Avyakta Kallam, Wajih Zaheer Kidwai, Dwight D. Kloth, Eric H. Kraut, Daniel Landsburg, Gary H. Lyman, Anjlee Mahajan, Ryan Miller, Victoria Nachar, Seema Patel, Shiven Patel, Lia E. Perez, Adam Poust, Fauzia Riaz, Rachel Rosovsky, Hope S. Rugo, Shayna Simon, Sumithira Vasu, Martha Wadleigh, Kelly Westbrook, Peter Westervelt, Ryan A. Berardi, Lenora Pluchino
Journal: Journal of the National Comprehensive Cancer Network (2022)

The NCCN Guidelines for Hematopoietic Growth Factors provide recommendations for the appropriate use of growth factors in the clinical management of febrile neutropenia (FN), chemotherapy-induced thrombocytopenia (CIT), and chemotherapy-induced anemia (CIA). Management and prevention of these sequelae are an integral part of supportive care for many patients undergoing cancer treatment. The purpose of these guidelines is to operationalize the evaluation, prevention, and treatment of FN, CIT, and CIA in adult patients with nonmyeloid malignancies and to enable the patient and clinician to assess management options for FN, CIT, and CIA in the context of an individual patient’s condition. These NCCN Guidelines Insights provide a summary of the important recent updates to the NCCN Guidelines for Hematopoietic Growth Factors, with particular emphasis on the incorporation of a newly developed section on CIT.
Abstract A028: Selective pressures on bone cancer evolution and treatment resistance emerging from the interactions with the bone ecosystem
Authors: David Basanta, Conor Lynch, Anna Miller, Ryan Bishop
Journal: Cancer Research (2022)

Abstract The bone is the organ of origin of several types of cancer including multiple myeloma, as well as a host to many metastatic lesions such as those characterizing prostate and breast cancer. The evolutionary dynamics that drive primary and metastatic progression in the bone, as well as those that explain the emergence of resistance to treatments such as proteosome inhibitors and hormonal deprivation therapies, result from the interactions between the tumor and the bone ecosystem. Models that can capture the complex ecological interactions in the bone are key to define the selective pressures underpinning somatic evolution in the bone. Our approach combines computational agent-based models with both in vitro and pre-clinical models in order to shed lights on some open questions in regard to tumor-stromal interactions. As well as the integration of biological and computational models, our approach is hypotheses-driven and captures the homeostasis of the bone that emerges from the interactions of key cellular species such as osteoblasts and osteoclasts. We have explored our models to investigate explore how prostate cancer cells can successfully initiate metastases in the bone, novel therapeutic approaches to treat bone metastatic prostate cancer, explore the emergence of treatment resistance in multiple myeloma and tease apart the contribution of environmentally-mediated drug resistance from cell-intrinsic resistance to proteosome inhibitors. Citation Format: David Basanta, Conor Lynch, Anna Miller, Ryan Bishop. Selective pressures on bone cancer evolution and treatment resistance emerging from the interactions with the bone ecosystem [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr A028.
Clinicobiological characteristics and treatment efficacy of novel agents in chronic lymphocytic leukemia with IGLV3-21R110
Authors: Paul J. Hengeveld, Y. Emre Ertem, Julie M. N. Dubois, Clemens H. M. Mellink, Anne-Marie van der Kevie-Kersemaekers, Ludo M. Evers, Kim Heezen, P. Martijn Kolijn, Olaf R. F. Mook, M. Mahdi Motazacker, Kazem Nasserinejad, S. Kersting, Peter E. Westerweel, Carsten U. Niemann, Arnon P. Kater, Anton W. Langerak, Mark-David Levin
Journal: Leukemia (2022)
Erratum to: Vascular histopathology and connective tissue ultrastructure in spontaneous coronary artery dissection: pathophysiological and clinical implications
Authors: Marios Margaritis, Francesca Saini, Ania A Baranowska-Clarke, Sarah Parsons, Aryan Vink, Charley Budgeon, Natalie Allcock, Bart E Wagner, Nilesh J Samani, Jan von der Thüsen, Jan Lukas Robertus, Mary N Sheppard, David Adlam
Journal: Cardiovascular Research (2022)
Successful biliary drainage in a patient with a giant hiatal hernia and pancreatic prolapse using the percutaneous–endoscopic rendezvous technique
Authors: Kosuke Iwano, Tatsuya Ishii, Tsuyoshi Hayashi, Toshifumi Kin, Akio Katanuma
Journal: Endoscopy (2022)

In patients who have a giant hiatal hernia, it is often difficult to advance a duodenoscope to the papilla of Vater [1]. In extremely rare cases of pancreatic prolapse into the thoracic cavity, endoscopic retrograde cholangiopancreatography (ERCP) is challenging because the orientation of the bile and pancreatic ducts is inverted [2] [3]. Herein, we report a case of successful biliary drainage, performed using the percutaneous–endoscopic rendezvous technique, in a patient with a giant hiatal hernia and pancreatic prolapse [4].
Identifying common transcriptome signatures of cancer by interpreting deep learning models
Authors: Anupama Jha, Mathieu Quesnel-Vallières, David Wang, Andrei Thomas-Tikhonenko, Kristen W Lynch, Yoseph Barash
Journal: Genome biology (2022)

Abstract Background Cancer is a set of diseases characterized by unchecked cell proliferation and invasion of surrounding tissues. The many genes that have been genetically associated with cancer or shown to directly contribute to oncogenesis vary widely between tumor types, but common gene signatures that relate to core cancer pathways have also been identified. It is not clear, however, whether there exist additional sets of genes or transcriptomic features that are less well known in cancer biology but that are also commonly deregulated across several cancer types. Results Here, we agnostically identify transcriptomic features that are commonly shared between cancer types using 13,461 RNA-seq samples from 19 normal tissue types and 18 solid tumor types to train three feed-forward neural networks, based either on protein-coding gene expression, lncRNA expression, or splice junction use, to distinguish between normal and tumor samples. All three models recognize transcriptome signatures that are consistent across tumors. Analysis of attribution values extracted from our models reveals that genes that are commonly altered in cancer by expression or splicing variations are under strong evolutionary and selective constraints. Importantly, we find that genes composing our cancer transcriptome signatures are not frequently affected by mutations or genomic alterations and that their functions differ widely from the genes genetically associated with cancer. Conclusions Our results highlighted that deregulation of RNA-processing genes and aberrant splicing are pervasive features on which core cancer pathways might converge across a large array of solid tumor types.
Concordance of Clinician-Documented and Imaging Response in Patients With Stage IV Non–Small Cell Lung Cancer Treated With First-Line Therapy
Authors: Xinran Ma, Lawrence Bellomo, Ian Hooley, Tori Williams, Meghna Samant, Katherine Tan, Brian Segal, Ariel Bulua Bourla
Journal: JAMA Network Open (2022)

<h3>Importance</h3> In observational oncology studies of solid tumors, response to treatment can be evaluated based on electronic health record (EHR) documentation (clinician-assessed response [CAR]), an approach different from standardized radiologist-measured response (Response Evaluation Criteria in Solid Tumours [RECIST] 1.1). <h3>Objective</h3> To evaluate the feasibility of an imaging response based on RECIST (IRb-RECIST) and the concordance between CAR and imaging response based on RECIST assessments, and investigate discordance causes. <h3>Design, Setting, and Participants</h3> This cohort study used an EHR-derived, deidentified database that included patients with stage IV non–small cell lung cancer (NSCLC) diagnosed between January 1, 2011, to June 30, 2019, selected from 3 study sites. Data analysis was conducted in August, 2020. <h3>Exposures</h3> Undergoing first-line therapy and imaging assessments of response to treatment. <h3>Main Outcomes and Measures</h3> In this study, CAR assessments (referred to in prior publications as "real-world response" [rwR]) were defined as clinician-documented changes in disease burden at radiologic evaluation time points; they were abstracted manually and assigned to response categories. The RECIST-based assessments accommodated routine practice patterns by using a modified version of RECIST 1.1 (IRb-RECIST), with independent radiology reads. Concordance was calculated as the percent agreement across all response categories and across a dichotomous stratification (response [complete or partial] vs no response), unconfirmed or confirmed. <h3>Results</h3> This study found that, in 100 patients evaluated for concordance, agreement between CAR and IRb-RECIST was 71% (95% CI, 61%-80%), and 74% (95% CI, 64%-82%) for confirmed and unconfirmed response, respectively. There were more responders using CAR than IRb-RECIST (40 vs 29 with confirmation; 64 vs 43 without confirmation). The main sources of discordance were the different use of thresholds for tumor size changes by RECIST vs routine care, and unavailable baseline or follow-up scans resulting in inconsistent anatomic coverage over time. <h3>Conclusions and Relevance</h3> In this cohort study of patients with stage IV NSCLC, we collected routine-care imaging, showing the feasibility of response evaluation using IRb-RECIST criteria with independent centralized review. Concordance between CAR and centralized IRb-RECIST was moderate. Future work is needed to evaluate the generalizability of these results to broader populations, and investigate concordance in other clinical settings.
Abstract B006: Evolutionary Tumor Board: Implementing dynamic personalized therapy using evolutionary theory and mathematical modeling for clinical decision support
Authors: Mark Robertson-Tessi, Joel Brown, Maria Poole, Kimberly Luddy, Andriy Marusyk, Jill Gallaher, Jeffrey West, Matthew Johnson, Heiko Enderling, Rikesh Makanji, Joaquim Farinhas, Robert Gatenby, Damon Reed, Christine Chung, Alexander Anderson
Journal: Cancer Research (2022)

Abstract This abstract is being presented as a short talk in the scientific program. A full abstract is available in the Proffered Abstracts section (PR010) of the Conference Proceedings. Citation Format: Mark Robertson-Tessi, Joel Brown, Maria Poole, Kimberly Luddy, Andriy Marusyk, Jill Gallaher, Jeffrey West, Matthew Johnson, Heiko Enderling, Rikesh Makanji, Joaquim Farinhas, Robert Gatenby, Damon Reed, Christine Chung, Alexander Anderson. Evolutionary Tumor Board: Implementing dynamic personalized therapy using evolutionary theory and mathematical modeling for clinical decision support [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr B006.
David Oliver: Protecting healthcare workers in future pandemics
Authors: David Oliver
Journal: BMJ (2022)

consultant in geriatrics and acute general medicineEarly in the pandemic, neither the NHS's clinical or ancillary staff nor social care workers were adequately protected from the risks of catching covid-19 in the course of their work.In the UK alone, hundreds of infected workers have died, thousands have been admitted to hospital, and tens of thousands have experienced long term effects. 1 -3 How do we improve staff protection next time?Here's my manifesto.We should ensure sufficient stockpiles of PPE throughout an outbreak, with adequate supply lines from trusted providers of high specification equipment.The contracting should be open and transparent, and due diligence should be applied in tendering.
Overall Survival with Palbociclib and Fulvestrant in Women with HR+/HER2− ABC: Updated Exploratory Analyses of PALOMA-3, a Double-blind, Phase III Randomized Study
Authors: Massimo Cristofanilli, Hope S. Rugo, Seock-Ah Im, Dennis J. Slamon, Nadia Harbeck, Igor Bondarenko, Norikazu Masuda, Marco Colleoni, Angela DeMichele, Sherene Loi, Hiroji Iwata, Ben O'Leary, Fabrice André, Sibylle Loibl, Eustratios Bananis, Yuan Liu, Xin Huang, Sindy Kim, Maria Jose Lechuga Frean, Nicholas C. Turner
Journal: Clinical Cancer Research (2022)

Abstract Purpose: To conduct an updated exploratory analysis of overall survival (OS) with a longer median follow-up of 73.3 months and evaluate the prognostic value of molecular analysis by circulating tumor DNA (ctDNA). Patients and Methods: Patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2−) advanced breast cancer (ABC) were randomized 2:1 to receive palbociclib (125 mg orally/day; 3/1 week schedule) and fulvestrant (500 mg intramuscularly) or placebo and fulvestrant. This OS analysis was performed when 75% of enrolled patients died (393 events in 521 randomized patients). ctDNA analysis was performed among patients who provided consent. Results: At the data cutoff (August 17, 2020), 258 and 135 deaths occurred in the palbociclib and placebo groups, respectively. The median OS [95% confidence interval (CI)] was 34.8 months (28.8–39.9) in the palbociclib group and 28.0 months (23.5–33.8) in the placebo group (stratified hazard ratio, 0.81; 95% CI, 0.65–0.99). The 6-year OS rate (95% CI) was 19.1% (14.9–23.7) and 12.9% (8.0–19.1) in the palbociclib and placebo groups, respectively. Favorable OS with palbociclib plus fulvestrant compared with placebo plus fulvestrant was observed in most subgroups, particularly in patients with endocrine-sensitive disease, no prior chemotherapy for ABC and low circulating tumor fraction and regardless of ESR1, PIK3CA, or TP53 mutation status. No new safety signals were identified. Conclusions: The clinically meaningful improvement in OS associated with palbociclib plus fulvestrant was maintained with &amp;gt;6 years of follow-up in patients with HR+/HER2− ABC, supporting palbociclib plus fulvestrant as a standard of care in these patients.
Issue 1 - “Update on adverse respiratory effects of outdoor air pollution” Part 2): Outdoor air pollution and respiratory diseases: Perspectives from Angola, Brazil, Canada, Iran, Mozambique and Portugal
Authors: A.C. Sousa, M.R. Pastorinho, M.R. Masjedi, M. Urrutia-Pereira, M. Arrais, E. Nunes, T. To, A.J. Ferreira, C. Robalo-Cordeiro, C. Borrego, J.P. Teixeira, L. Taborda-Barata
Journal: Pulmonology (2022)

To analyse the GARD perspective on the health effects of outdoor air pollution, and to synthesise the Portuguese epidemiological contribution to knowledge on its respiratory impact. Ambient air pollution has deleterious respiratory effects which are more apparent in larger, densely populated and industrialised countries, such as Canada, Iran, Brazil and Portugal, but it also affects people living in low-level exposure areas. While low- and middle-income countries (LMICs), are particularly affected, evidence based on epidemiological studies from LMICs is both limited and heterogeneous. While nationally, Portugal has a relatively low level of air pollution, many major cities face with substantial air pollution problems. Time series and cross-sectional epidemiological studies have suggested increased respiratory hospital admissions, and increased risk of respiratory diseases in people who live in urban areas and are exposed to even a relatively low level of air pollution. Adverse respiratory effects due to air pollution, even at low levels, have been confirmed by epidemiological studies. However, evidence from LMICs is heterogeneous and relatively limited. Furthermore, longitudinal cohort studies designed to study and quantify the link between exposure to air pollutants and respiratory diseases are needed. Worldwide, an integrated approach must involve multi-level stakeholders including governments (in Portugal, the Portuguese Ministry of Health, which hosts GARD-Portugal), academia, health professionals, scientific societies, patient associations and the community at large. Such an approach not only will garner a robust commitment, establish strong advocacy and clear objectives, and raise greater awareness, it will also support a strategy with adequate measures to be implemented to achieve better air quality and reduce the burden of chronic respiratory diseases (CRDs).
Polymer based sustained drug delivery to the ocular posterior segment: barriers and future opportunities for the treatment of neovascular pathologies
Authors: Rasha A. Alshaikh, Christian Waeber, Katie B. Ryan
Journal: Advanced Drug Delivery Reviews (2022)

There is an increasing momentum in research and pharmaceutical industry communities to design sustained, non-invasive delivery systems to treat chronic neovascular ocular diseases that affect the posterior segment of the eye including age-related macular degeneration and diabetic retinopathy. Current treatments include VEGF blockers, which have revolutionized the standard of care for patients, but their maximum therapeutic benefit is hampered by the need for recurrent and invasive administration procedures. Currently approved delivery systems intended to address these limitations exploit polymer technology to regulate drug release in a sustained manner. Here, we critically review sustained drug delivery approaches for the treatment of chronic neovascular diseases affecting the ocular posterior segment, with a special emphasis on novel and polymeric technologies spanning the spectrum of preclinical and clinical investigation, and those approved for treatment. The mechanism by which each formulation imparts sustained release, the impact of formulation characteristics on release and foreign body reaction, and special considerations related to the translation of these systems are discussed.
Mammals and Mutations, Life Span, Cancer Risk
Journal: Cancer Discovery (2022)

Findings from the Wellcome Sanger Institute in Hinxton, UK, indicate that across 16 mammalian species, somatic mutation rates per year appear to strongly influence life span. Another study of 191 mammalian species, led by the University of Montpellier in France, shows that cancer mortality risk is associated with diet but independent of body mass and life span, confirming the validity of Peto's paradox.